Method for producing the tautomeric form of (1) of 2,4,6-trianilino-p-(carbo-1′-ethylhexyl-1′oxyl)-1, 3, 5-triazine

ABSTRACT

The invention relates to a method for producing the tautomeric form (I) of 2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine by the crystallization of a tautoner mixture in the presence of one or more solvents selected from the group consisting of aliphatic alcohol having 2 8 C-atoms made of aliphatic alcohol, aliphatic carboxylic acid alkyl esters having a total of between 3–10 C-atoms, aromatic carboxylic acid alkyl esters having a total of between 8–12 C-atoms, aliphatic carboxylic acid esters having a total of between 3 9 C-atoms, carboxylic acid nitriles having a total of between 2–8 C-atoms, dialkylketones having a total of between 3–6 C-atoms and aliphatic sulphones having a total of between 3–6 C-atoms. The solvent or solvent mixture can additionally contain up to 30 wt % of a hydrocarbon (I) acts as a light protecting agent in cosmetic preparations.

The present invention relates to a novel process for the preparation ofthe tautomeric form I of2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine

by crystallization from a tautomer mixture.

The invention also relates to the use of the form I isolated in this wayas light protection agent in cosmetic preparations.

EP-B 087 098 (1) describes the preparation of2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine fromcyanuric chloride and 2-ethylhexyl p-aminobenzoate, and the purificationof the crude product by recrystallization from petroleum spirit.

DE-A 35 18 670 (2) relates to the use of esters of a branched alkanoicacid having 6 to 10 carbon atoms and a saturated aliphatic alcoholhaving 10 to 20 carbon atoms as solvent in the preparation of s-triazinederivatives such as2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′oxy)-1,3,5-triazine.

The products which form in said processes are generally tautomermixtures, as can be readily deduced from the relevant IR spectra. It isknown, for example from J. Elguero, C. Marzin, A. R. Katritzky and P.Linda, Advances in Heterocyclic Chemistry, Supplement 1, The Tautomerismof Heterocycles, Academic Press New York, 1976, Ch. 2, p. 168, that inthe case of amino-s-triazine derivatives, tautomers with regard to theNH protons can generally arise.

The use of the2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine tautomermixtures obtained in this way in cosmetic preparations often leads tothe problem of the substance which has passed into solution in thecosmetic oils used gradually settling out again upon storage.

In addition, it is important for the user that the substance ischemically uniform during the test for its suitability for theapplication and during the application itself. Particularly fortoxicological investigations and compatibility tests, the results ofwhich are naturally of particular relevance for ingredients of cosmeticpreparations, mixtures of substances of varying physical properties,i.e. including tautomer mixtures, cannot be used because in feedingexperiments with them on living organisms in these test organisms noconstant composition can be presupposed, meaning that the result ofthese tests could consequently be falsified. In addition, such mixturesare often subject to great variation in the composition due to evenminute changes to the preparation conditions, meaning that a certaincomposition can only be reproduced with difficulty.

It is an object of the present invention to overcome the disadvantagesdescribed when using2,4,6-trianilino-p-(carbo-2′ethylhexyl-1′-oxy)-1,3,5-triazine.

We have found that this object is achieved by a process for thepreparation of the tautomeric form I of2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine bycrystallization from a tautomer mixture in the presence of one or moresolvents chosen from the group consisting of aliphatic alcohols having 2to 8 carbon atoms, aliphatic carboxylic alkyl esters having a total of 3to 10 carbon atoms, aromatic carboxylic alkyl esters having a total of 8to 12 carbon atoms, aliphatic carbonic esters having a total of 3 to 9carbon atoms, carbonitriles having a total of 2 to 8 carbon atoms,dialkyl ketones having a total of 3 to 6 carbon atoms and aliphaticsulfones having a total of 3 to 6 carbon atoms, where the solvent or thesolvent mixture may additionally comprise up to 30% by weight of ahydrocarbon.

Suitable aliphatic alcohols having 2 to 8 carbon atoms arestraight-chain, branched alcohols and also cyclic alcohols. Exampleswhich may be mentioned are ethanol, n-propanol, isopropanol, n-butanol,tert-butanol, n-pentanol, n-hexanol, n-octanol, 2-ethylhexanol andcyclohexanol. An alcohol which is preferably used as solvent is ethanol.

Suitable aliphatic carboxylic alkyl esters having a total of 3 to 10carbon atoms are, for example, straight-chain carboxylic esters, such asethyl formate, n-propyl formate, methyl acetate, ethyl acetate, n-propylacetate, n-butyl acetate, methyl butyrate, ethyl butyrate, n-propylbutyrate and n-butyl butyrate. Preference is given to aliphaticcarboxylic alkyl esters having a total of 3 to 6 carbon atoms,particularly to ethyl acetate.

Aromatic carboxylic alkyl esters having a total of 8 to 12 carbon atomsare to be understood as meaning, for example, methyl benzoate, ethylbenzoate, n-propyl benzoate, isopropyl benzoate, n-butyl benzoate,tert-butyl benzoate, preferably methyl benzoate.

Aliphatic carbonic esters having a total of 3 to 9 carbon atoms whichmay be mentioned are dimethyl carbonate, diethyl carbonate, di-n-propylcarbonate, diisopropyl carbonate, di-n-butyl carbonate and propylenecarbonate, preferably dimethyl carbonate.

Suitable carbonitriles having a total of 2 to 8 carbon atoms are, forexample, acetonitrile, propionitrile, n-butyronitrile, benzonitrile,preferably acetonitrile.

Suitable dialkyl ketones having a total of 3 to 6 carbon atoms are,inter alia, straight-chain, branched and cyclic dialkyl ketones, forexample acetone, butanone, 2-pentanone, 3-pentanone, 2-hexanone,3-hexanone and cyclohexanone, preferably acetone.

A representative of aliphatic sulfones having a total of 3 to 6 carbonatoms which may be mentioned is, for example, tetramethylene sulfone.

The hydrocarbons optionally coused as cosolvent can either be aliphatichydrocarbons, such as pentane, hexane, petroleum ether, ligroin orcyclohexane and/or aromatic hydrocarbons, such as toluene or xylene.These hydrocarbons can be present in an amount up to 30% by weight,preferably in an amount of not more than 10% by weight.

A preferred embodiment of the process according to the inventioninvolves the crystallization being carried out in one of the aliphaticalcohols having 2 to 4 carbon atoms mentioned at the start, in one ofthe aliphatic carboxylic alkyl esters having a total of 3 to 6 carbonatoms mentioned at the start, or a mixture thereof.

The crystallization is particularly preferably carried out in ethanol,ethyl acetate or a mixture thereof as solvent.

The solvents used for the purposes of the present invention can eitherbe anhydrous or else have a water content of at most 10% by weight,preferably of at most 5% by weight, particularly preferably of at most2% by weight. This is true in particular for the abovementionedaliphatic alcohols and for the aliphatic carboxylic alkyl esters.

The recrystallization is generally carried out by dissolving thetautomer mixture in the solvent or the solvent mixture at temperaturesof from 40 to 120° C., preferably 60 to 100° C. The amount of solvent isexpediently 100 to 2000% by weight, preferably 150 to 600% by weight,based on the tautomer mixture. After insoluble components have beenfiltered off at elevated temperature, the couse of filtrationauxiliaries being advisable, the tautomeric form I is separated off bycrystallization at temperatures of from approximately 15 to 40° C. SinceI tends to form supersaturated solutions, the addition of seed crystalsis expedient at this temperature. Filtration, drying and optionallyformulation are carried out in accordance with customary methods.

The tautomer mixture used is expediently admixed directly as a melt withsaid solvent or solvent mixture. However, the tautomer mixture can alsobe introduced into the hot solvent in crystallized form or can be heatedtogether with this solvent.

The tautomeric form I is stable as such and, in solid and in dissolvedform, does not convert back to the tautomer mixture.

BRIEF DESCRIPTION OF THE DRAWINGS.

FIGS. 1 and 2 show a characteristic range of the IR spectrum of thetautomeric form I.

FIG. 3 shows the IR spectrum of the tautomoric miflure in the samerange.

The present invention further provides for the use of the tautomericform I isolated in this way as light protection agent in cosmeticpreparations. Examples of the compositions of such cosmeticpreparations, such as light protection emulsions, oil-in-water lightprotection creams, water-in-oil light protection creams or lightprotection foams are given in the patent specification (1).

Customary cosmetic oils which are used as solvent for I are, in additionto the C₆–C₁₀-alkanoic acid C₁₀–C₂₀-alkyl esters, which form the basisof the patent publication (2), such as cetylstearyl 2-ethylhexanoate,for example groundnut oil, olive oil, isopropyl stearate, isopropylmyristate, coconut fatty acid triglycerides, caprylic-caprictriglyceride, triethyl citrate, polyethylene glycol glyceryl cocoate,diisopropyl adipate, propoxylated myristyl alcohol or mixtures thereof.The solubilities of the tautomeric form I in said cosmetic oils issufficiently high. The storage stability of these solutions with regardto clouding and precipitation is significantly better because thesolutions remain clear over a prolonged period.

A further advantage of the process according to the invention is thegood crystallizability and, associated therewith, the good filterabilityand good drying behavior of the tautomerically pure product.

EXAMPLE 1 Preparation of the Tautomeric Form I by Recrystallization fromEthanol

250 kg of s-trichlorotriazine (corresponding to 1.36 kmol) were reactedwith 1025 kg of 2-ethylhexyl p-aminobenzoate (corresponding to 4.11kmol) in xylene as solvent to give the2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine tautomermixture.

After the solvent had been distilled off, 4500 kg of ethanol(corresponding to 400% by weight, based on the tautomer mixture used)were added to the 115° C.-hot melt over the course of 5 to 6 hours, thetemperature being maintained between 65 and 80° C. Following theaddition of 25 kg of a customary filtration auxiliary (Celite®),insoluble components were filtered off at 65 to 70° C. and the solutionwas cooled to 20° C. Then, by seeding with 150 kg of the tautomeric formI (coarsely crystalline, undried product from an earlier batchcorresponding to 110 kg of dry product), crystallization was initiated.After stirring for 18 hours at 20° C., the product was discharged via acentrifuge, washed with ethanol and dried at 60° C./20 mbar. This gave915 kg of tautomerically pure I (72% yield, based on s-trichlorotriazineused and after deducting the amount of seed crystal).

The IR spectrum of the product (KBr pellet) showed, in the range of thecarbonyl stretching vibrations, only one band for the carboxyl groups at1697 cm⁻¹ (see FIG. 1) in contrast to the corresponding double band forthe product from Comparative Example A.

EXAMPLE 2 Preparation of the Tautomeric Form I by Recrystallization fromEthyl Acetate

Analogously to Example 1, the recrystallization was carried out with400% by weight of ethyl acetate, based on the tautomer mixture used. Thetautomerically pure product was obtained in a yield of 58%.

The IR spectrum of the product (KBr pellet) showed, in the range of thecarbonyl stretching vibrations, only one band for the carboxyl groups at1697 cm⁻¹ (see FIG. 2) in contrast to the corresponding double band forthe product from Comparative Example A.

EXAMPLES 3 TO 12

Analogously to Example 1, the recrystallization was carried out in eachcase with ethylhexanol (Ex. 3), cyclohexanol (Ex. 4), methyl benzoate(Ex. 5), tetramethylenesulfone (Ex. 6), dimethyl carbonate (Ex. 7),methyl ethyl ketone (Ex. 8), acetonitrile (Ex. 9) and acetone (Ex. 10),and with solvent mixtures of 90% by weight of ethanol/10% by weight ofxylene (Example 11) and 90% by weight of ethyl acetate/10% by weight ofxylene (Example 12).

The IR spectra of the products isolated in each case (KBr pellet)likewise showed, in the range of the carbonyl stretching vibrations,only one band for the carboxyl groups at 1697 cm⁻¹.

COMPARATIVE EXAMPLE A Recrystallization from Petroleum Spirit

According to the patent specification (1), the tautomer mixture producedin the preparation was recrystallized from petroleum spirit with boilinglimits from 120 to 130° C.

The IR spectrum of the product (KBr pellet) shows, in the range of thecarbonyl stretching vibrations, a double band for the carbonyl groups at1717/1694 cm⁻¹ (see FIG. 3), which is to be regarded as proof of thepresence of two tautomeric forms. The IR spectrum for the tautomermixture prior to recrystallization was essentially identical to thisspectrum.

EXAMPLE 13 Storage Stability of Solutions of the Tautomeric Form I inCosmetic Oils

The tautomerically pure compound I was dissolved in each case inC₈–C₁₀-coconut fatty acid triglyceride (solubility 5.8 g per 100 g ofoil) and cetylstearyl 2-ethylhexanoate (solubility 1.0 g per 100 g ofoil). Both solutions were still clear after 2 days.

By contrast, corresponding initially clear solutions of the tautomermixture with a widely varying content of I became cloudy after just 1day, and precipitations were evident after just 2 days.

1. A process for the preparation of the tautomeric form I of2,4,6-trianilino-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine

by crystallization from a tautomer mixture in the presence of one ormore solvents chosen from the group consisting of aliphatic alcoholshaving 2 to 8 carbon atoms, aliphatic carboxylic alkyl esters having atotal of 3 to 10 carbon atoms, aromatic carboxylic alkyl esters having atotal of 8 to 12 carbon atoms, aliphatic carbonic esters having a totalof 3 to 9 carbon atoms, carbonitriles having a total of 2 to 8 carbonatoms, dialkyl ketones having a total of 3 to 6 carbon atoms andaliphatic sulfones having a total of 3 to 6 carbon atoms, where thesolvent or the solvent mixture may additionally comprise up to 30% byweight of a hydrocarbon.
 2. A process as claimed in claim 1, wherein thecrystallization is carried out in an aliphatic alcohol having 2 to 4carbon atoms, in an aliphatic carboxylic alkyl ester having a total of 3to 6 carbon atoms or a mixture thereof.
 3. A process as claimed in claim1, wherein the crystallization is carried out in ethanol, ethyl acetateor a mixture thereof.